The catalytic enantioselective construction of all-carbon quaternary centers represents a considerable challenge in synthetic organic chemistry.[1,2] A new carbon-carbon bond must be formed in the face of significant steric hindrance to accomplish this goal.
Synthetic methods for the generation of quaternary stereocenters are extremely desirable given their prevalence in a broad variety of biologically active natural products.[2] Despite their importance, the number of highly enantioselective transformations that construct quaternary stereocenters under mild reaction conditions is limited. The palladium-catalyzed decarboxylative asymmetric allylic alkylation is a powerful and reliable approach to bridge this gap.[3]
However, despite the importance of palladium-catalyzed decarboxylative asymmetric alkylation in total synthesis, its application on an industrial scale is often hampered by the need for high catalyst loadings (5.0-10.0 mol %). The high cost of palladium significantly increases the cost of each reaction. Furthermore, high catalyst loadings also increase the risk of poisoning downstream chemistry or contaminating active pharmaceutical ingredients.[4]
These drawbacks have discouraged application of the enantioselective allylic alkylation on a larger scale. The application of transition metal catalysis to industry-scale synthesis requires transformations that are safe, robust, cost-effective, and scalable.[5] Consequently, there remains a significant need to develop new reaction protocols that employ lower catalyst concentrations and hence facilitate the scale-up of such transformations.